This research aims to define and develop hapten-specific suppression of anti-nucleic acid antibody formation, to develop an approach to the therapy of SLE, and to establish a well-characterized system for the study of tolerance mechanisms involving a naturally occurring antigen that is important in auto-immune disease. Nucleosides, nucleotides, and oligodeoxyribonucleotides, including short helical forms, will be conjugated to isologous IgG to form tolerogens. They will be tested against immunization by matching hemocyanin-hapten conjugates and by denatured DNA-methylated BSA complexes. The optimal determinants for a wide range of NZB/NZW and SLE sera will be defined. IgG conjugates of these haptens will be tested for suppression of disease in NZB/NZW mice. Antibody responses and tolerance induction will be tested in several strains of mice to explore the genetic control of susceptibility to tolerance induction. Haptens will be conjugated to erythrocytes to provide target cells for assays of hapten-specific plaque-forming cells in responding and tolerant animals, so that the cellular mechanisms of tolerance may be explored.